Identification of the antigenic stimulus of immunoglobulin synthesis in the rheumatoid synovium. 1) Radioactively labeled IgG, newly synthesized in cultures of surgically excised synovial tissues from patients with rheumatoid arthritis (RA), will be tested for its selective binding to a spectrum of human viral antigens. 2) Extending studies in experimental antigen-induced arthritis (Cooke et al, this laboratory), human cartilage and tendon obtained at the time of surgical synovectomy or prosthetic joint replacement will be examined as potential reservoirs for antigen-antibody complexes since release of antigen from such complexes could explain the chronic nature of RA. Chemical extraction and dissociation of these complexes may allow isolation of sufficient antigen to permit its detection by selective binding to labeled-IgG from synovial cultures. Role of cellular immunity in RA. Incorporation of H3-thymidine into PHA-stimulated lymphocytes in the synovium will be measured by an organ culture method for synovial fragments recently developed in this laboratory. Increased incorporation induced by PHA would reflect stimulation of lymphocytes of thymic origin. 2) Tissue fragments and suspensions of lymphocytes from RA synovium or synovial fluid will be examined for cell surface immunoglobulin receptors to gain information about the type of lymphocytes present. 3) RA peripheral blood lymphocyte cytotoxicity for synovial fibroblasts in vitro will also be examined, and the possible masking of this immunity by introduction of serum blocking factors of the type described by the Hellstroms, investigated.